Tremendous progress has been made in obtaining an understanding of the control of glycogenolysis and gluconeogenesis in perfused livers and isolated hepatocytes. Knowledge of the control of these processes in the live exercising animal or human subject is somewhat limited. Factors which determine the rate of hepatic glycogenolysis and gluconeogenesis during exercise will be investigated. The following specific questions will be addressed: Is liver cAMP-dependent protein kinase activated during exercise? Are adrenal medullary hormones essential for stimulation of liver glycogenolysis at high work rates? At what plasma concentration does epinephrine influence the liver glycogenolytic rate during exercise? Is the cAMP response and liver glycogenolytic rate higher in female or juvenile rats (which have a preponderance of beta-adrenergic receptors in liver) than in adult male rats (which have a preponderance of alpha-adrenergic receptors). In these studies the glycogenolytic rate will be quantitated in livers of rats run on a rodent treadmill. Stress hormones and factors known to influence the glycogenolytic rate will be quantitated. The effect of adrenodemedullation and of epinephrine infusion at rates designed to span the physiologic range will be studied with respect to control of the hepatic glycogenolytic rate. The roles of fructose-2,6-bisphasphate and of epinephrine and insulin in controlling the rate of gluconeogenesis in fasted running rats will also be investigated. These studies should not only contribute to our understanding of the basic control of hepatic glucose production during exercise, but also will provide a better basis for recommendation of exercise programs for athletes, armed forces personnel, for individuals with metabolic diseases such as diabetes, and for the increasing numbers of our population who exercise for health and recreation.